This proposal is concerned with the determinants of sleep apnea. Specifically, the proposal investigates a recently identified phenomenon referred to as long-term facilitation (LTF). Long-term facilitation (LTF) occurs following repetitive hypoxic stimulation. This mechanism may stabilize respiration during sleep. Three specific aims will be investigated: 1) To determine why LTF of ventilation occurs in snorers but not in non-snorers; 2) To determine whether LTF results in increased pharyngeal caliber and amelioration of inspiratory flow limitation; 3) To determine whether LTF is present in sleep apnea patients. The questions addressed in this proposal are of great public health significance given the prevalence of sleep-disordered breathing. Human subjects spanning the spectrum of susceptibility to upper airway closure will be studied during natural sleep. Specific Aim 1 will test two hypotheses: 1) Inspiratory resistive loading and attendant hypoventilation contribute to the development of LTF. To this end, the development of LTF after CPAP unloading in snorers or inspiratory resistive loading in non-snorers will be determined; 2) LTF occurs in snorers because of increased chemoreceptor stimuli owing to hypoventilation. The occurrence of LTF will be tested under hypercapnic and hypocapnic conditions. Specific Aim 2 will test the hypothesis that LTF is activated preferentially at the level of UA dilators lending to increased UA dilator activity, decreased upper airway resistance, and collapsibility. Upper airway resistance and the maximum plateau flow will be measured during room air control and the recovery period following repetitive hypoxia. Specific Aim 3 will ascertain whether patients with sleep apnea lack LTF. The presence/absence of LTF under baseline conditions and after 4 weeks of therapy with nasal CPAP will be investigated. If LTF is absent at baseline, the follow-up study will determine whether this is a primary or secondary effect.